Recent studies here demonstrate that glucan, a Beta 1,3 polyglucose from bakers yeast has significant value in enhancing both non-specific and specific resistance against Leishmania donovani. Injection of glucan alone, either before or after infection, results in significantly lower parasite burdens in organs of mice and importantly, in highly susceptible hamsters. Simultaneous intravenous inoculation of glucan with formalin-killed promastigotes confers resistance in mice challenged with viable parasites 21, 40 or 80 days after immunization. Injections of killed promastigotes alone provides no protection. It is especially important to note that a preliminary experiment indicates that a similar immunization protocol elicits resistance against L. donovani in hamsters. We also found that immunization with a glucan-dead promastigote regimen via intraperitoneal or subcutaneous routes enhanced resistance of mice against infection. Using methods presently employed here we intend to define optimum conditions for generation of resistance against L. donovani and L. braziliensis using killed promastigotes in combination with glucan. These studies specifically address (a) optimum minimal stimulation necessary to elicit measurable responsiveness against infection, (b) comparison of immunization routes with emphasis on potential extrapolative value for human use, i.e. subcutaneous and intramuscular, (c) duration of immunication-induced resistance, (d) methods of killed promastigote preparation to provide a practical means of vaccine storage and shipment, (e) mechanisms of vaccine-induced immunity with special attention directed at methods with value in predicting immune status before challenge. Response mechanisms pertinent to induced resistance will be studied with emphasis on humoral and cell mediated responsiveness. Those mechanisms will also be examined via interaction of parasites and macrophages in a culture system. Our studies have provided the first evidence that immunization with dead parasites may be a feasible method for eventual control of visceral leishmaniasis. The proposed research, to define optimum conditions for vaccine-induced immunity against L. donovani and L. braziliensis, can have significant medical impact.